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Biomedical subjects

A House

Publications and source records attributed to A House.

At least 19 recordsLinked to original sources
PubMed2001

Effect of tachykinins on airway function in cynomolgus monkeys.

Tachykinins have been implicated as important mediators of asthma. This study used neurokinin A (NKA) and substance P (SP) to evaluate the effect of tachykinins on airway mechanics in cynomolgus monkeys. NK(1)-(CP 99,994) and NK(2)-(SR 48968) receptor antagonists were used to evaluate the role of NK(1)and NK(2)receptors on responses to NKA and SP. Lung resistance (R(L)) and dynamic lung compliance (C(Dyn)) were measured in anesthetized, mechanically ventilated cynomolgus monkeys following aerosol or intravenous challenge with NKA, SP or the standard bronchoconstrictor, histamine. Inhaled NKA or SP had variable effects on R(L)and C(Dyn)whereas aerosolized histamine (0.01-1 mg/ml) dose-dependently increased R(L)and decreased C(Dyn). Intravenous NKA (1-100 microg/kg), SP (1-30 microg/kg) or histamine (1-100 microg/kg) increased R(L)and decreased C(Dyn). Pretreatment with SR 48968 (0.1 and 1 mg/kg, i.v.) blocked bronchoconstrictor responses to i.v. NKA, whereas CP 99,994 (0.1 and 1 mg/kg, i.v.) was without effect. Bronchoconstrictor responses to i.v. SP were partially blocked by SR 48968 and CP 99,994. In conclusion, both NKA and SP produce bronchonconstriction in cynomolgus monkeys and this effect is more pronounced when they are given by the iv route. Furthermore, both NK(1)and NK(2)receptors are involved in the bronchonconstrictor response to exogenously administered tachykinins in cynomolgus monkeys.

Administration, Inhalation↗
PubMed2001

Bronchoconstrictor reactivity to NKA in allergic dogs: a comparison to histamine and methacholine.

Airway hyperresponsiveness to neurokinin A (NKA) occurs in inflammatory airway diseases like asthma. In this study, bronchoconstrictor reactivity to NKA was measured in beagle dogs neonatally sensitized to and challenged with ragweed. Comparisons were made to histamine and methacholine. Lung resistance (R(L)) and dynamic lung compliance (C(Dyn)) were measured in anesthetized, spontaneously breathing dogs before and after aerosol challenge with NKA, histamine or methacholine. The concentration of these agents increasing R(L)by 25% above baseline (PC(25)) was calculated before and 24 h after aerosolized ragweed challenge. Before ragweed, the bronchoconstrictor reactivity to NKA was four-fold higher in ragweed-sensitized dogs (PC(25)=0.036+/-0.006%) compared to non-sensitized controls (PC(25)=0.177+/-0.030%, P<0.05). On the other hand, there was no difference in the bronchoconstrictor reactivity to histamine or methacholine between these two groups. Twenty-four hours after ragweed challenge to sensitized dogs, NKA reactivity was unchanged from pre-ragweed values but histamine and methacholine reactivity was increased by 2-3-fold. These results demonstrate airway hyperresponsiveness to NKA, histamine and methacholine in allergic beagle dogs although hyperresponsiveness to NKA exists in these allergic dogs before an antigen challenge. This animal model may prove to be useful to evaluate the role of tachykinins in hyperractive airway diseases.

Administration, Inhalation↗
PubMed2001

Atresia of the distal external acoustic meatus in a Bouvier des Flandres.

A five-year-old male Bouvier des Flandres was presented with chronic otalgia of approximately four and a half years' duration. Atresia of the external acoustic meatus was diagnosed. A total ear canal ablation and bulla osteotomy were performed. All symptoms of otalgia resolved within two weeks of surgery.

Animals↗
PubMed2001

Mortality at 12 and 24 months after stroke may be associated with depressive symptoms at 1 month.

BACKGROUND AND PURPOSE: Previous studies have reported mood symptoms after stroke to be a risk factor for later mortality. The purpose of the study was to examine whether mood symptoms at 1 month after stroke may be a risk factor for mortality at 12 and 24 months. METHODS: As a cohort within a randomized controlled trial, 448 hospital patients were seen at 1 month after stroke and were randomized into a trial of psychological therapy. Follow-up was at 12 and 24 months. Mood symptoms were assessed by the Present State Examination and the General Health Questionnaire (GHQ)-28. Measures of disability before and after stroke and of cognitive impairment after stroke were also taken at 1 month. Mortality was determined at 12 and 24 months after stroke. RESULTS: In logistic regression analyses, mortality at 12 months was associated unifactorally with scoring on the GHQ-D subscale (odds ratio [OR] 2.4, 95% CI 1.3 to 4.5) and scoring in the highest quartile of the GHQ (OR 3.1, 95% CI 1.1 to 8.8). In multiple logistic regression analyses, only GHQ-D remained a significant predictor after controlling for other known predictors. At 24 months, scoring on GHQ-D (OR 2.4, 95% CI 1.4 to 4.1) and in the highest GHQ quartile (OR 2.2, 95% CI 1.0 to 4.8) was significantly associated with mortality in unifactoral analyses. Scoring on the GHQ-D remained a predictor of mortality after controlling for other variables. Psychiatric disorder, such as major depression (according to International Classification of Diseases, 10th Revision), was not statistically significantly associated with increased mortality at 12 or 24 months. CONCLUSIONS: Mood symptoms on a self-reported rating scale were associated with 12- and 24-month mortality after stroke, after adjustment for factors associated with stroke severity. The result is in keeping with other evidence that depressive symptoms are a risk factor for death from vascular disease.

Aged↗
PubMed2000

Depression after stroke and lesion location: a systematic review.

BACKGROUND: There is conflicting evidence on the hypothesis that the risk of depression after stroke is influenced by the location of the brain lesion. We undertook a systematic review to examine the hypotheses that depression is more commonly associated with left-hemisphere strokes than with right-hemisphere strokes and with lesions of the left anterior brain than with other regions. METHODS: We did a computer-aided search of MEDLINE, BIDS ISI, and PsychLit databases supplemented by hand searches of key journals. We included all reports on the association of depression after stroke with the location of the brain lesion. Studies were systematically and independently examined by two investigators. Fixed-effects and random-effects meta-analyses were done. FINDINGS: 143 reports were identified by the search strategy. 48 were eligible for inclusion. Not all reports included original data. Only two reports of original data supported the hypotheses and seven clearly did not. The pooled (random-effects) relative risk of depression after a left-hemisphere stroke, compared with a right-hemisphere stroke, was 0.95 (95% CI 0.83-1.10). For depression after a left anterior lesion compared with all other brain areas the pooled (random-effects) relative risk was 1-17 (0.87-1.62). Restriction of the analyses to reports from high-quality studies or major depressive disorder did not substantially affect the findings. Nor were they affected by stratification of the time between stroke and the assessment of depression. Multiple publications from the same samples of patients were apparent. INTERPRETATION: This systematic review offered no support for the hypothesis that the risk of depression after stroke is affected by the location of the brain lesion.

Aphasia↗
PubMed2000

Psychosocial versus pharmacological treatments for deliberate self harm.

OBJECTIVES: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. SEARCH STRATEGY: Electronic databases screened: MEDLINE (from 1966-February 1999); PsycLit (from 1974-March 1999); Embase (from 1980-January 1999); The Cochrane Controlled Trials Register (CCTR) No.1 1999. Ten journals in the field of psychiatry and psychology were hand searched for the first version of this review. We have updated the hand search of three specialist journals in the field of suicidal research until the end of 1998. Reference lists of papers were checked and trialists contacted. SELECTION CRITERIA: All RCTs of psychosocial and/or psychopharmacological treatment versus standard or less intensive types of aftercare for patients who shortly before entering a study engaged in any type of deliberately initiated self-poisoning or self-injury, both of which are generally subsumed under the term deliberate self-harm. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports independently by two reviewers. Studies were categorized according to type of treatment. The outcome measure used to assess the efficacy of treatment interventions for deliberate self-harm was the rate of repeated suicidal behaviour. We have been unable to examine other outcome measures as originally planned (e.g. compliance with treatment, depression, hopelessness, suicidal ideation/thoughts, change in problems/problem resolution). MAIN RESULTS: A total of 23 trials were identified in which repetition of deliberate self-harm was reported as an outcome variable. The trials were classified into 11 categories. The summary odds ratio indicated a trend towards reduced repetition of deliberate self-harm for problem-solving therapy compared with standard aftercare (0.70; 0.45 to 1.11) and for provision of an emergency contact card in addition to standard care compared with standard aftercare alone (0.45; 0.19 to 1.07). The summary odds ratio for trials of intensive aftercare plus outreach compared with standard aftercare was 0.83 (0.61 to 1.14), and for antidepressant treatment compared with placebo was 0.83 (0. 47 to 1.48). The remainder of the comparisons were in single small trials. Significantly reduced rates of further self-harm were observed for depot flupenthixol vs. placebo in multiple repeaters (0. 09; 0.02 to 0.50), and for dialectical behaviour therapy vs. standard aftercare (0.24; 0.06 to 0.93). REVIEWER'S CONCLUSIONS: There still remains considerable uncertainty about which forms of psychosocial and physical treatments of self-harm patients are most effective, inclusion of insufficient numbers of patients in trials being the main limiting factor. There is a need for larger trials of treatments associated with trends towards reduced rates of repetition of deliberate self-harm. The results of small single trials which have been associated with statistically significant reductions in repetition must be interpreted with caution and it is desirable that such trials are also replicated.

Cognitive Behavioral Therapy↗
PubMed2000

The timing of acts of deliberate self-harm: is there any relation with suicidal intent, mental disorder or psychiatric management?

OBJECTIVE: To investigate the common perception that more serious suicide attempts tend to occur earlier in the day. METHODS: Prospective study of 158 adults referred for psychiatric assessment from the general hospital following an episode of deliberate self-harm. The main outcome measures used were Beck's Suicide Intent score, ICD-10 psychiatric diagnosis, alcohol consumption at the time of the attempt, and follow-up decision recorded by the interviewing duty psychiatrist. The patient also completed a checklist of current precipitating problems. RESULTS: A marked circadian variation in timing of the act was found, peaking between 2200 and 2400 h. "Early" acts (0300-1459 h) were significantly less likely to involve alcohol consumption, more likely to lead to admission to a medical ward, and involved more patient-identified problems than "late" acts. People who took overdoses early in the day were more likely to have concerns about their own mental health. Compared to earlier acts of self-harm, late evening (2200-2359 h) cases were less likely to be diagnosed as depressed or offered psychiatric follow up. No relation was found between time of day of self-harm and Beck's Suicide Intent score. CONCLUSIONS: Implications arise regarding clinical risk assessment and current staffing levels in the accident and emergency department. The interviewing psychiatrist could concentrate on excluding depression and teaching problem solving to those who self-harm in the morning or afternoon, and on the detection and treatment of alcohol dependence for late evening cases.

Adolescent↗
PubMed2000

Deliberate self poisoning with antidepressant drugs: a comparison of the relative hospital costs of cases of overdose of tricyclics with those of selective-serotonin re-uptake inhibitors.

BACKGROUND: Debate continues over the relative merits of tricyclics and selective serotonin re-uptake inhibitors (SSRIs) as first line antidepressant treatment for depression. SSRIs are safer in overdose but more expensive than tricyclics. This report compared the hospital costs of cases of overdose with both groups of drug. METHODS: Records of all persons aged over thirteen years presenting to a general hospital in one year were analysed for demographic information and details of their attendance. RESULTS: There were 1165 episodes of self-poisoning, 151 involving tricyclics as the sole antidepressant and 69 SSRIs as the sole antidepressant. Those taking SSRIs had a shorter (1.96 vs. 2.59 days) and less expensive ( pound330 vs. pound567) stay. A large proportion of this difference in cost was due to a small number of admissions to the Intensive Care Unit. LIMITATIONS: This study used only hospital costs, so excluding costs associated with primary care. CONCLUSIONS AND CLINICAL RELEVANCE: If there were similar cost differences countrywide, the difference in hospital costs of self poisoning with SSRIs and tricyclics would represent an additional pound3.87 million per year due to self poisoning with tricyclics across the whole of England and Wales. This is a small proportion of the estimated pound100 million cost of switching to first-line prescribing of SSRIs for depression.

Adolescent↗
PubMed2000

Psychiatric illness predicts poor outcome after surgery for hip fracture: a prospective cohort study.

BACKGROUND: Hip fracture is common in the elderly. Previous studies suggest that psychiatric illness is common and predicts poor outcome, but have methodological weaknesses. Further studies are required to address this important issue. METHODS: We prospectively recruited 731 elderly participants with hip fracture in two Leeds hospitals. Psychiatric diagnosis was made within 5 days of surgery using the Geriatric Mental State schedule and other standardized instruments, and data on confounding factors was collected. Main study outcomes were length of hospital stay, and mortality over 6 months after fracture. RESULTS: Fifty-five per cent of participants had cognitive impairment (dementia in 40% and delirium in 15%), 13% had a depressive disorder, 2% had alcohol misuse and 2% had other psychiatric diagnoses. Participants were likely to remain in hospital longer if they suffered from dementia, delirium or depression. The relative risks of mortality over 6 months after hip fracture were increased in dementia and delirium, but not in depression. CONCLUSIONS: Psychiatric illness is common after hip fracture, and has significant effects on important outcomes. This suggests a need for randomized, controlled trials of psychiatric interventions in the elderly hip fracture population.

Aged↗
PubMed2000

Anxiety in cancer patients.

Anxiety is common in cancer patient populations, and must often initially be recognized and managed by cancer care professionals. This article reviews the recent oncology and mental health literature on anxiety. The aim is to help those involved in cancer patient care who are not specialists in mental health to understand the nature of anxiety, and discriminate morbid from normal anxiety. We review recent research into the association of anxiety with events during diagnosis and management of cancer, highlighting the importance of the meaning of events to an individual as an important factor in making people anxious. Lastly we review management strategies which might be used by cancer care professionals, in particular the importance of an awareness of specific patterns of communication which may alleviate or maintain anxiety for some cancer patients.

Anti-Anxiety Agents↗
PubMed1999

Stressful life events and difficulties and onset of breast cancer: case-control study.

OBJECTIVE: To determine the relation between stressful life events and difficulties and the onset of breast cancer. DESIGN: Case-control study. SETTING: 3 NHS breast clinics serving west Leeds. PARTICIPANTS: 399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents. MAIN OUTCOME MEASURES: Odds ratios of the risk of developing breast cancer after experiencing one or more severe life events, severe difficulties, severe 2 year non-personal health difficulties, or severe 2 year personal health difficulties in the 5 years before clinical presentation. RESULTS: 332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1. 81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump. CONCLUSION: These findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.

Adult↗
PubMed1999

Hypermethylation of the MYF-3 gene in colorectal cancers: associations with pathological features and with microsatellite instability.

Myf-3 is the human homologue of the murine Myo-D1 gene involved in muscle-cell differentiation. Using Southern blot analysis, we examined methylation of Myf-3 in histologically normal colonic mucosae, adenomas and carcinomas from a large series of patients with primary colorectal cancer. Hypermethylation of this gene in comparison with normal mucosa was observed in 88% of adenomas and in 99% of carcinomas. The pattern of Myf-3 methylation was similar in different areas of the same tumour, suggesting that methylation imbalances occur before the bulk of clonal-cell expansion. Significantly increased levels of Myf-3 methylation were observed in tumours which were more invasive, located in the proximal colon or from older patients. Patients whose tumours had extensive methylation showed a trend for shortened survival, though this was probably related to their being more invasive. Extensive methylation was significantly more frequent in tumours with microsatellite instability. Further work is required to determine whether the hypermethylation of Myf-3 observed in colorectal cancers is a specific alteration with functional significance or whether it reflects non-specific methylation imbalances occurring early during tumorigenesis.

Adenoma↗
PubMed1999

Pre-operative chemoradiotherapy in locally advanced rectal cancer.

BACKGROUND: The aim of the present study was to investigate the effectiveness and toxicity of pre-operative chemoradiation in locally advanced rectal cancer (T3-T4). METHODS: Forty-seven patients were assessed (38 T3 and nine T4 tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy in 25 fractions over 5 weeks. Bolus 5-fluorouracil (5-FU) was delivered 500 mg/m2 on days 1, 2, 3 and days 22, 23, 24. Total mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4-6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. RESULTS: All patients undergoing chemoradiation completed therapy as planned, with no treatment-related interruptions. The regimen had a low acute toxicity profile with an estimated 50% or greater response in 38 out of 47 patients (four patients had complete responses). Forty-three (97%) of 44 patients who underwent surgery were operable. Patients who were operated on between 4 and 7 weeks had a statistically better response then those who were operated on after 7 weeks (P = 0.013; Fisher's exact test). Eight of 10 patients who were considered to be inoperable prior to the treatment underwent total mesorectal excision with negative radial margins. Anastomotic leakage occurred in four patients (9%); one required surgical intervention. Wound infection occurred in three patients (6%); one patient required re-exploration for haemorrhage. Delayed complications occurred in three patients (6%); one requiring surgery for a stomal stricture. After a median follow-up of 20 months, two patients (4%) had developed local recurrence. CONCLUSION: The pre-operative chemoradiation regimen employed had a low acute toxicity profile and all patients completed therapy. The majority of patients considered inoperable prior to receiving this treatment underwent successful excision. Appropriately fractionated pre-operative chemoradiotherapy is a reasonable option in this disease and deserves further evaluation.

Adenocarcinoma↗